The long term objective of the proposal is to understand the signaling pathways and in vivo functions of heterotrimeric proteins G12 and G13. The project contains two major parts. The first part will use established mouse embryonic fibroblast cell lines from different G-protein knockout mice to dissect G-protein coupled receptor (GPCR) specificity. Two specific aims are included in this parts. Aim 1: Complete the study of G- protein pathways linked to G2A, novel GPCR: Aim 2: Study the specificity of other novel GPCRs. The second part of the proposal will concentrate on in vivo functions of G13 and G12 in angiogenesis. Five specific aims are included in the second part. Aim 1: Compare the integrity of endothelial cell and smooth muscle cell development of wild type and Ga13-/- mice from E8.0 to E9.5. Aim 2: The capability of endothelial cells isolated from both wild type and G13 mutant embryos to form capillary-like structure will be examined in vitro. The possible differences of these endothelial cells in adhesion and migration will also be compared. Aim 3. Compare the difference of vascular smooth muscle cells between wild type and mutant G13 mice, especially their ability to migrate under PDGF and HB-EGF. Aim 4: Examine the different mechanisms of embryonic death observed in Ga12-/Ga13-/-, Ga12-/- Ga13+/-, and Ga12+/+Ga13-/- mice. Aim 5: Tissue-Specific knockout mice will be used to test the possible defects observed in the above studies.